Sulfuric Acid → Methyl 1-(4-fluorophenyl)-6-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 1048879Notes

Reaction equation

HRID 1048879 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=3)[C:11](=[O:19])[C:10]([C:20]([OH:22])=[O:21])=[CH:9]2)=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[C:28](=O)(O)[O-].[Na+]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=3)[C:11](=[O:19])[C:10]([C:20]([O:22][CH3:28])=[O:21])=[CH:9]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 1214479811-(4-Fluorophenyl)-6-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Product 1

HCID 121447947Methyl 1-(4-fluorophenyl)-6-hydroxy-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 74%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Compound K (383 mg, 1.28 mmol, 1.00 eq) was dissolved in methanol (6.4 mL) and concentrated sulfuric acid (0.64 mL) was added dropwise. The reaction was heated to reflux for 3 hours at which point it was cooled and neutralized with a saturated solution of sodium bicarbonate. The mixture was extracted with a solution of 3:1 CHCl3:IPA (2×) and the combined organics were dried (MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel using 0-20% 89:10:1 DCM:methanol:NH40H afforded 296 mg (74%) of the title compound as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.36 (s, 1H), 7.72-7.68 (m, 2H), 7.61 (d, J=2.8 Hz, 1H), 7.49 (t, J=8.7 Hz, 2H), 7.11 (dd, J=9.0, 2.8 Hz, 1H), 6.84 (d, J=9.1 Hz, 1H), 3.71 (s, 3H); ES-MS [M+1]+: 314.2.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 3 hours at which point it
  3. temperaturewas cooled
  4. extractionThe mixture was extracted with a solution of 3:1 CHCl3
  5. dry with materialIPA (2×) and the combined organics were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography on silica gel using 0-20% 89:10:1 DCM

Sources & evidence

ORD record
ord-e23b5e801d8e45babcb90cc57dc8a0a2
Source dataset
uspto-grants-2016_07
Patent number
US09382208B1

Reaction notes

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